We will develop analytic tools for the pharmacokinetic study of racemic drugs in human subjects with the synthesis of carbon-13 (stable isotope) labeled optical enantiomers, with their detection and quantitation in blood, urine, and stool by mass spectrometry. The direct study of the pharmacologic activity and metabolic disposition of racemic warfarin will be undertaken by labelling each enantiomer with C13-isotope and combining each C13-labeled enantiomer with the opposite C12-enantiomer. Each C13/C12-racemate will be administered to the subjects and both the hypoprothrombinemia and the metabolic fate of each enantiomer will be quantitated in blood, urine, and stool. Some drug interactions with racemic mixtures are stereospecific. To determine the stereospecificity of the interaction of warfarin with phenylbutazone, barbiturates, and metronidazole, the subjects will receive a single-dose or 21-day course of C13/C12-racemic warfarin with and without a course of the interacting drug and the usual parameters serially quantitated. We will quantitate the interaction of racemic warfarin with rifampin, vitamin E, and spironolactone with high-pressure liquid chromatographic separation in plasma, urine, and stool of unchanged warfarin and its metabolites.